Depression part 2

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http://stressedanddepressed.ca/book...-cannabis-as-an-antidepressant-and-stimulant/

Cross-Cultural Use​

Humans brought cannabis with them wherever they migrated (Robinson, 1996). Von Bibra (1855/1995, p. 150) wrote that hashish confections eaten by the Turks caused them to become “cheerful, to sing, laugh, and to make all kinds of merry follies”. In India, the antidepressant effects of cannabis are some of the most well-known, and the plant has been used in central Asia as an antidepressant for centuries (Rubin, 1976). According to researchers studying users in Jamaica, cannabis “makes you feel happy” (Rubin & Comitas, 1976, p. 127). Working class males in Jamaica note an energizing effect (Rubin, 1976), as do the Iroquois, who use cannabis as a stimulant – they claim “this plant will get you going” (Moerman, 1998, p. 136). Carter wrote in 1980 (as cited in Fride & Russo, 2006, p. 374) that in Costa Rica smokers use cannabis as a remedy for depression and malaise, as do the Shamans of Nepal who continue to use cannabis as an antidepressant to this day (Rätsch, 1998/2001, p. 18). Schnelle, Grotenhermen, Reif, and Gorter (1999) reported in a study of 128 German-speaking medical cannabis users that depression was the most common reason (12%) cited for self-medicating with cannabis. Swift, Gates, and Dillon (2005) found similar, but even stronger results in an Australian study of 128 medical cannabis users. They reported that 56% of their participants used cannabis for depression. These kinds of results substantiate what the overall historical and global evidence tell us. After a massive review of the historical and cross-cultural evidence of the medicinal use of cannabis, Rätsch (1998/2001, p. 178) writes; “Around the world, hemp is particularly valued as an antidepressant. From a medical perspective, this mood-enhancing ability may be hemp’s most important effect”. Dr. Tod Mikuriya, psychiatrist and world-renowned cannabis expert, came to the same conclusion based on the evidence and his own clinical practice, calling cannabis’ ability to fight depression “…perhaps its most important property” (as cited in Gieringer et al., 2008, p. 83).

Recent Studies​

Modern scientific studies continue to substantiate the observations of ancient cultures, while showing a more nuanced interaction between the consumer and the plant. A World Health Organization (WHO) study included the following statement: “There are also reports of an anti-depressant effect, and some patients may indeed use cannabis to ‘self-treat’ depressive symptoms, but these need to be better evaluated” (WHO, 1997, p. 28). These findings were bolstered by Grant and Pickering (1998) in a U.S. epidemiological study investigating the relation between levels of cannabis use and cannabis abuse and dependence, commenting “…cannabis might be used to self-medicate major depression” (p. 255). Gieringer et al. (2008, p. 83) assert that “[m]any psychiatric patients who do not respond well to standard treatment find marijuana beneficial for depression”. In addition, multiple studies fail to find an association between cannabis use and depression, despite rigorous design, statistical power, and methodology (see Denson & Earleywine, 2006 for the studies). However, a study of 17 subjects at Duke University found that cannabis smoking actually increased depression – but only among inexperienced users (Mathew, Wilson, & Tant, 1989). A follow-up study (Mathew, Wilson, Humphreys, Lowe, & Wiethe, 1992) did not produce any adverse effects. The authors argue that this is likely because adverse effects are most often associated with novice users, and although the participants were infrequent users, they did have experience. In addition, dose plays a role in the positive versus negative effects of cannabis, as do age of first use and level of use. For example, Degenhardt, Hall, and Lynskey (2003) did find a modest association between cannabis use and depression in a review of the literature, but only among problematic and heavy users. Degenhardt et al. (2003) also found a modest association in several studies between early onset use, regular use, and later depression, even when potential confounding variables were controlled for. Hayatbakhsh et al. (2007) found that the association between age of onset, level of use, and later depression was strongest for those who initiated use before age 15. A more recent epidemiological study using more than 85,000 participants from 17 countries found a similar association (de Graaf et al., 2010). However, it is important to note that at least one longitudinal study following participants from preschool through age 18 found that those who experimented with drug use during their adolescence (up to once a month, almost exclusively with cannabis), were the best adjusted, both psychologically and socially, compared to both frequent users and abstainers (Shedler & Block, 1990). It is also important to keep in mind that correlation does not equal causation. In fact, emerging evidence suggests that accounting for childhood traumas such as sexual abuse may diminish the association between cannabis use and psychosis, and therefore, researchers investigating the association between cannabis use and psychiatric disorders should adjust their analyses to account for this potentially confounding variable (Houston, Murphy, Shevlin, & Adamson, 2011). A recent review of the literature by Fride and Russo (2006) demonstrated the complexity of the topic, reporting that cross-sectional studies tend to show that depression leads to the use of cannabis while longitudinal studies tend to show the converse and that in non-clinical samples, either weak or no associations are found between several measures of depression and cannabis smoking. Furthermore, although a significantly higher number of suicide attempts was reported in cannabis smokers in one study, once several confounding factors were controlled for, the association disappeared. Thus, the authors conclude that, “…taken together, the epidemiological evidence does not support a causative or precipitating role for cannabis in chronic depression or anxiety” (Fride & Russo, 2006, p. 376).

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Indeed, the opposite may be true. Importantly, a study of 79 psychotics found that those who used cannabis recreationally reported less anxiety, depression, insomnia and physical discomfort (Warner et al., 1994). In fact, emerging evidence strongly suggests that cannabidiol, one of the other most well-known cannabinoids, is a potent antipsychotic. For example, a phase II clinical trial on the effects of cannabidiol in schizophrenia and schizophreniform psychosis revealed that cannabidiol was as effective as amisulpride, a standard antipsychotic in Europe and Australia and available in Canada through the Special Access Program but not available in the United States, in reducing acute psychosis symptoms, but with far fewer negative side effects (Canadian Agency for Drugs and Technologies in Health, 2011; Kaplan, 2004; Lecrubier et al., 2001; Leweke et al., 2005). Other studies substantiate these findings (e.g., Zuardi et al., 2006; Zuardi & Guimaraes, 1997). Researchers have identified the cannabinoid delta-9-tetrahydrocannabinol (THC) as a primary source of the stimulating, euphoric, and antidepressant effects of cannabis (Rätsch, 1998/2001, p. 6), and after investigating the potential effects of cannabinoids on depression, Musty (2002) reported participants had feelings of euphoria, but no anxiety from the use of cannabis. Furthermore, an internet survey of 4,400 adults by researchers at the University of Southern California found that cannabis users reported less depressed mood and more positive affect than non-users (Denson & Earleywine, 2006). In fact, evidence is mounting that major depression, along with other psychiatric disorders, may be associated with a dysfunctional endocannabinoid system (e.g., Ashton & Moore, 2011; Pacher et al., 2006), and therefore, it is not surprising that studies continue to find that depression is one of the leading reasons cited for the use of cannabis (e.g., Swift et al., 2005). There is also a well-known association between chronic illness and depression, such as the development of depression due to pain caused by Multiple Sclerosis, and that the alleviation of the pain also leads to the alleviation of depression. For instance, a recent Canadian study concluded, “…results support the claim that smoked cannabis reduces pain, improves mood and helps sleep” (Ware et al., 2010, p. E701). Further support for the antidepressant effects of cannabis and the cannabinoids comes from a surprising source. In 2007, rimonabant, a CB1receptor blocker developed as an anti-obesity drug by French company Sanofi-Aventis under the trade name Acomplia®, was denied FDA approval by the U.S. because it was linked to increased depression, suicidal thoughts, suicide attempts, suicide events, anxiety, and insomnia (Badawi, n.d.; Gieringer et al., 2008). Considering the evidence strongly suggesting the antidepressant effects of cannabis, as well as the known mechanisms of action of the cannabinoids and the homeostatic role the endocannabinoid system plays, it should not be surprising that blocking one of the main receptors for the cannabinoids would lead to these adverse events. Of particular importance in this discussion is the fact that the federal Medical Marihuana Access Regulations in Canada already allow for the use of cannabis for depression, among other psychiatric conditions, so long as the appropriate form (i.e., Form B2) is completed by a qualified medical professional (Health Canada, 2005, 2007). The situation in the United States is a little bit more complicated because they do not have a federal medical cannabis program. However, to date sixteen states and the District of Columbia have enacted their own laws to legalize cannabis for medical purposes, and of those, thirteen leave room for the use of cannabis for depression and/or other psychiatric conditions by including medical conditions whose primary symptoms include depression, such as Post Traumatic Stress Disorder, by allowing the use of cannabis for any chronic or persistent medical condition that limits a person’s ability to perform one or more major life activities or if not alleviated, could cause serious mental or physical harm to the patient, or by allowing the use of cannabis for any number of unspecified medical conditions upon the approval of the various state Departments of Health (California Senate Bill 420, 2003; ProCon.org, 2011). However, despite the evidence and both federal and state programs allowing for the use of cannabis for depression, it is acknowledged that treating “…depression with cannabis may be difficult because of differences in individual makeup, need for continuous dose levels, expense, availability, and illegality” (Mikuriya, 1998).

Comparisons With Synthetic Medicines​

Lester Grinspoon, retired Harvard Medical professor and world-renowned cannabis expert who specialized in the study and treatment of schizophrenia, reported that cannabis compares favorably in both efficacy and safety to many pharmaceutical antidepressants (Grinspoon & Bakalar, 1993). Moreover, numerous independent assessments of the safety, efficacy, and dependence potential of cannabis clearly indicate that cannabis and cannabis-based medications are well-tolerated, non-toxic, cannot lead to death by overdose, and are unlikely to lead to dependence in the vast majority of patients. For instance, the Institute of Medicine’s 1999 report, Marijuana and Medicine: Assessing the Science Base, in relation to the safety of cannabis, noted: “The side effects of cannabinoid drugs are within the acceptable risks associated with approved medications” (Joy, Watson, & Benson, 1999, p. 127). In addition, in 1988 the Drug Enforcement Agency’s Chief Administrative Law Judge, Francis Young, after two years of hearing expert testimony and reviewing thousands of documents concluded: A smoker would theoretically have to consume nearly 1,500 pounds of marijuana within about 15 minutes to induce a lethal response. In practical terms, marijuana cannot induce a lethal response as a result of drug-related toxicity….In strict medical terms marijuana is far safer than many foods we commonly consume. For example, eating 10 raw potatoes can result in a toxic response. By comparison, it is physically impossible to eat enough marijuana to induce death. Marijuana in its natural form is one of the safest therapeutically active substances known to man. By any measure of rational analysis marijuana can be safely used within the supervised routine of medical care. (pp. 57-59) Sadly, the same safety and efficacy profile cannot be said to exist for the majority of pharmaceutical antidepressants, with well-known court cases and science establishing the very real and dangerous side-effects of drugs like the commonly prescribed Serotonin Specific Reuptake Inhibitors (SSRIs) (Degroot, 2008; Kauffman, 2009). For instance, it is well established that during the early stages of treatment with SSRIs that anxiety is actually likely to increase, and that certain populations are at increased risk of suicide or self-harm (Degroot, 2008; Kauffman, 2009). As a result, to reduce these potential side effects, early treatment with SSRIs is often combined with the use of drugs like benzodiazapines (which have a list of their own serious negative side effects) (Degroot, 2008; Longo & Johnson, 2000). Furthermore, along with a host of physical and psychological complaints (Degroot, 2008; Kauffman, 2009), the potential side effects of SSRIs may include homicide and suicide (Kauffman, 2009). In fact, case precedence has established that murder and suicide are potential side effects of SSRI use and the manufacturer can be, and has been, held liable (Kauffman, 2009; see http://ssristories.com/index .php for a list of violent incidents and court cases associated with SSRI use). Neither of these outcomes has been shown to be causally associated with the use of cannabis (Price, Hemmingsson, Lewis, Zammit, & Allebeck, 2009; Reiss & Roth, 1993). To compound the problem, it may very well be that millions of patients are not only being prescribed a more dangerous medication than cannabis, but that most of them are deriving no benefit while shouldering substantial risks. For example, Kirsch, Moore, Scoboria, and Nicholls (2002) analyzed both published and unpublished clinical trials submitted to the U. S. Food and Drug Administration (FDA) on the six most commonly prescribed SSRIs and found that placebo control groups duplicated about 80% of the response to medication. In 2008, Kirsch, Deacon, et al. conducted a meta-analysis on data submitted to the FDA on four new-generation antidepressant medications. They found that the medications were ineffective in treating patients with moderate and even severe depression, with only minor clinical improvements in the most severely depressed. It is important to note that emerging evidence demonstrates that many patients are turning to cannabis to safely and effectively reduce and/or replace synthetic antidepressants after having grown tired of the negative side effects associated with their use. For example, in examinations of 2,480 California patients, Dr. Mikuriya found that 27% reported using cannabis for “mood disorders” and another 5% used cannabis as a substitute for more toxic drugs (Gieringer, 2002). A recent survey of doctors in California found “that many of their patients were able to decrease their use of…antidepressant, antianxiety, and sleeping medications, or else they use cannabis to treat their side effects of jitteriness or gastrointestinal problems in order to stay on their medications” (Holland, 2010, p. 285). Currently, the most comprehensive study ever conducted in Canada investigating the barriers medical cannabis users encounter while trying to gain access to their medication of choice is underway (see https://www.surveymonkey.com/s/CannabisSurvey). The survey includes several questions about cannabis as a substitute for both illicit drugs and prescribed pharmaceuticals.

Cannabis as Preventive Medicine​

Those studying the plant and its uses throughout world cultures, as well as human history, have observed the ability of cannabis and the cannabinoids to prevent illness, and not just treat symptoms, for some time. For instance, in 1845 in relation to the use of hashish and its effects, Moreau wrote, “I report them here only to call attention to the prophylactic action [emphasis added] of a substance that could offer valuable therapeutic resources” (Moreau, 1845/1973, p. 213). More recently, after an extensive review of the then extant literature, Mikuriya (1969) made a list of the medical uses for cannabis, under the title of Possible Therapeutic Applications of Tetrahydrocannabinols and Like Products. The list included “Prophylactic [emphasis added] and treatment of the neuralgias, including migraine and tic douloureux….Antidepressant-tranquilizer [emphasis added]” (p. 39). Even more recently, Dr. Dreher, nurse, anthropologist, and dean of nursing at Rush University Medical Centre, in an interview about her research into prenatal exposure to cannabis and neonatal outcomes in Jamaica had the following to say about the importance of cultural context and the preventive properties of cannabis: American drug use often takes place without cultural rules and in an unsupervised context. The Jamaican women we studied had been educated in a cultural tradition of using marijuana as a medicine. They prepared it with teas, milk and spices, and thought of it as apreventive and curative substance[emphasis added].…Some of these women were in dire socioeconomic straits, and they found that smoking ganja helped allay feelings of worry and depression [emphasis added] about their financial situation. (Brady, 1998, “Is it possible that American women…”) Rätsch (1998/2001), writing about the use of cannabis in Jamaica amongst Rastafarians noted that: [h]emp tea is a popular drink for preventiveuse [emphasis added] and is also consumed therapeutically for almost all ailments. Hemp preparations are often ingested forprophylactic purposes [emphasis added]. The frequent use does not just protect from diseases, but also gives courage and strength…(p. 140). It is important to note that one can also infer the preventive medicine properties of cannabis by taking a step back and, instead of focusing on one or two narrow medical conditions for which cannabis may be used, recognizing the sheer volume of and widely disparate chronic and acute medical conditions and/or symptoms for which cannabis has already been proven effective in treating, for which accumulating evidence strongly suggests cannabis is effective in treating, and for which preliminary research shows cannabis is potentially effective in treating. These varied and serious medical conditions and symptoms include, but are not limited to, nausea and vomiting, wasting syndromes associated with AIDS and cancer, multiple sclerosis, amyotrophic lateral sclerosis, spinal cord diseases and injuries, epilepsy and other seizure disorders, a variety of chronic pain conditions (e.g., migraine, fibromyalgia, rheumatoid arthritis, neuropathy), a variety of movement disorders, glaucoma, a variety of psychiatric disorders, a variety of inflammatory diseases, and various cancers (e.g., Fride & Russo, 2006; Grinspoon, Bakalar, & Russo, 2005; Guzmán, 2003; Health Canada, 2010; Russo, 2001). A rational analysis of the body of evidence demonstrating the ability of a single substance, cannabis, to treat or potentially treat such a wide variety of medical conditions and symptoms through its actions on the endocannabinoid system, which acts as a bodily homeostatic regulator, very strongly suggests that cannabis likely plays a role in delaying the progression of and/or preventing many illnesses when used properly. However, perhaps the most powerful evidence of the preventive properties of cannabis and the cannabinoids comes from the U.S. government itself. In 2003 the government, as represented by the Department of Health and Human Services, was awarded patent number 6630507, entitled Cannabinoids as Antioxidants and Neuroprotectants. The abstract states, in part, that cannabinoids are “…useful in the treatment and prophylaxis [emphasis added] of wide variety of oxidation associated diseases, such as ischemic, age-related, inflammatory and autoimmune diseases” (Hampson, Axelrod, & Grimaldi, 2003, Abstract section).

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Beginning to Understand the Nuances of Cannabis Medicine​

Cannabis has paradoxical effects, having for instance both relaxing and stimulating effects. However, these effects are based upon many factors, including the strain of cannabis, the quality, potency, and purity of the strain, number of types and ratios of cannabinoids, number of types and ratios of terpenes (compounds that produce the unique aromas and tastes of individual strains, but which have their own proven therapeutic properties and which act synergistically with the cannabinoids), dose, and the health, setting, mindset, and diet of the user, as well as the user’s experience with and tolerance to the various cannabinoids (e.g., Gieringer et al., 2008; McPartland & Russo, 2006; Russo, 2011). These factors, influencing the effects of cannabis upon its consumers, have been known for quite some time. For instance, in The National Dispensatory of 1894, it is written that “the plants richest in resin grow at an altitude of 1800 to 2400 m” (Stillé et al., p. 393) and that the effect of cannabis “varies with the individual’s temperament” (Stillé et al., p. 395). In Cushny’s 1906 Pharmacology and Therapeutics or the Actions of Drugs the effects of cannabis are described as: …a mixture of depression and stimulation…its action…seems to depend very largely on the disposition and intellectual activity of the individual. The preparations used also vary considerably in strength, and the activity of even the crude drug seems to depend very largely on the climate and season in which it is grown, so that great discrepancies occur in the account of its effects. (p. 232) One text notes that “[p]reparations made from plants grown in warm climates are usually better” (Blumgarten, 1932, p. 338). Another notes that after two years of storage “…it had lost about half its potency” (Osol & Farrar, 1947, p. 1382). Still another notes that “[m]any of the psychological effects seem related to the setting in which the drug is taken” (Holvey et al., 1972, p. 1415). One even noted “…an occasional panic reaction has occurred, particularly in naive [sic] users, but these have become unusual as the culture has gained increasing familiarity with the drug” (Berkow et al., 1982, p. 1427). Another noted that cannabis’ effects are dependent upon “the dose of the drug and the underlying psychological conditions of the user” (Venes et al., 2001, p. 1242). Unfortunately, the prohibition of cannabis had a negative effect on its medicinal reputation. Textbooks began to remark upon the “completely unpredictable” nature of the drug (Faddis, 1943, p. 153), or its unreliability in providing consistent results (“Cannabis”, 1952; Dilling, 1933) – blaming the drug itself for the researchers’ and cultivators’ lack of understanding of the proper cultivation, storage, and transportation of cannabis for medicine, the various strains, their types and ratios of cannabinoids and the effects of each on the user, and the importance of the subject’s mindset and setting within which cannabis is consumed. Some textbooks then began omitting entirely any mention of cannabis in their later editions (e.g., Blumgarten, 1940; Pierce, 1935). Others began to falsely blame whole-plant cannabis for the effects experienced by one of its isolated, synthesized, and concentrated cannabinoids, particularly THC (Gieringer et al., 2008; Wade & Reynolds, 1977). This is of particular importance because the evidence is mounting that several cannabinoids, as well as the terpenoids and flavonoids present in whole-cannabis, are important, and they act synergistically to enhance some of the positive effects and to reduce some of the negative effects of cannabis use, such as the cognitive impairment associated with THC (e.g., Gieringer et al., 2008; Russo, 2011; Russo & Guy, 2006; Russo, Guy, & Robinson, 2007). Still, the special relationship between cannabis’ prohibition and its reputation as a dangerous or unpredictable drug was accurately assessed in the 1987 Merck Manual of Diagnosis and Therapy: “…the chief opposition to the drug rests on a moral and political, and not a toxicological, foundation” (Berkow et al., 1987, p. 1490). The numerous studies and commissioned reports conducted since 1987, some of which call for the outright legalization and regulation of cannabis (e.g., Senate Special Committee on Illegal Drugs of 2002), but which have been ignored, only reinforce this conclusion.

What About the Smoke?​

We understand that many health-care professionals are reluctant to recommend cannabis to their patients due to the potential pulmonary damage from smoking whole cannabis. However, despite what many believe about harms associated with smoking cannabis, the best available evidence strongly suggests that it does not lead to lung cancer. In fact, the evidence strongly suggests that the cannabinoids offer a protective factor against the development of several kinds of cancer (see for example Guzmán, 2003). For more detailed information about this topic, as well as other cannabis myths, please refer to the free series of informative articles at www.stressedanddepressed.ca. That being said, the harms associated with smoking cannabis can be mitigated or eliminated through harm reduction techniques such as vaporizing or ingesting cannabis (see for example Earleywine & Van Dam, 2010). For more detailed information about this, please refer to the free series of informative articles at www.stressedanddepressed.ca.

Conclusion​

Thus, despite current fears that the use of cannabis leads to depression, when all the evidence is considered together and taken in context, it is clear that cannabis has been used safely and effectively as an antidepressant and mild stimulant for thousands of years, continues to be used for those purposes by many cultures all over the world, and modern science corroborates those uses, when used properly. Therefore, it can be asserted that cannabis has antidepressant and stimulant properties. If, after reviewing the evidence surrounding its safety, cannabis is found to pose an acceptable risk for medical use, it should be considered by physicians as a legitimate treatment option for those who are currently dealing with depression and/or fatigue, as well as for thosewho wish to avoid – or, in the case of current users, continue to avoid – these serious conditions.

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For more on the history of cannabis as a medicine, information on its proper use to reduce potential harm, and evidence to disprove common myths, please refer to For Membership and Access to Cannabis for Medical Purposes, Please Come and See Us at 1353 East 41st Avenue, Vancouver BC V5W 1R1 or visit us online at www.stressedanddepressed.ca.